Emerging regulatory paradigms in glutathione metabolism

Yilin Liu, Annastasia S. Hyde, Melanie A. Simpson, Joseph J. Barycki

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites and highlight remaining questions about molecular details of the accepted regulatory modes.

Original languageEnglish (US)
Pages (from-to)69-101
Number of pages33
JournalAdvances in Cancer Research
Volume122
DOIs
StatePublished - 2014

Fingerprint

Glutathione
Neoplasms
Enzymes
Metabolic Networks and Pathways
Oxidation-Reduction
Buffers
Oxidative Stress

Keywords

  • 5-Oxoprolinase
  • ChaC1
  • Glutamate cysteine ligase
  • Glutathione
  • Glutathione synthetase
  • Redox homeostasis
  • γ-Glutamyl cycle
  • γ-Glutamylcyclotransferase
  • γ-Glutamyltranspeptidase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Emerging regulatory paradigms in glutathione metabolism. / Liu, Yilin; Hyde, Annastasia S.; Simpson, Melanie A.; Barycki, Joseph J.

In: Advances in Cancer Research, Vol. 122, 2014, p. 69-101.

Research output: Contribution to journalArticle

Liu, Yilin ; Hyde, Annastasia S. ; Simpson, Melanie A. ; Barycki, Joseph J. / Emerging regulatory paradigms in glutathione metabolism. In: Advances in Cancer Research. 2014 ; Vol. 122. pp. 69-101.
@article{14df33b809154b3aa460e5b4775b1403,
title = "Emerging regulatory paradigms in glutathione metabolism",
abstract = "One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites and highlight remaining questions about molecular details of the accepted regulatory modes.",
keywords = "5-Oxoprolinase, ChaC1, Glutamate cysteine ligase, Glutathione, Glutathione synthetase, Redox homeostasis, γ-Glutamyl cycle, γ-Glutamylcyclotransferase, γ-Glutamyltranspeptidase",
author = "Yilin Liu and Hyde, {Annastasia S.} and Simpson, {Melanie A.} and Barycki, {Joseph J.}",
year = "2014",
doi = "10.1016/B978-0-12-420117-0.00002-5",
language = "English (US)",
volume = "122",
pages = "69--101",
journal = "Advances in Cancer Research",
issn = "0065-230X",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Emerging regulatory paradigms in glutathione metabolism

AU - Liu, Yilin

AU - Hyde, Annastasia S.

AU - Simpson, Melanie A.

AU - Barycki, Joseph J.

PY - 2014

Y1 - 2014

N2 - One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites and highlight remaining questions about molecular details of the accepted regulatory modes.

AB - One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites and highlight remaining questions about molecular details of the accepted regulatory modes.

KW - 5-Oxoprolinase

KW - ChaC1

KW - Glutamate cysteine ligase

KW - Glutathione

KW - Glutathione synthetase

KW - Redox homeostasis

KW - γ-Glutamyl cycle

KW - γ-Glutamylcyclotransferase

KW - γ-Glutamyltranspeptidase

UR - http://www.scopus.com/inward/record.url?scp=84902984780&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902984780&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-420117-0.00002-5

DO - 10.1016/B978-0-12-420117-0.00002-5

M3 - Article

VL - 122

SP - 69

EP - 101

JO - Advances in Cancer Research

JF - Advances in Cancer Research

SN - 0065-230X

ER -